FR143166 attenuates spinal pain transmission through activation of the serotonergic system

• Published in: European journal of pharmacology Vol. 452; no. 3; pp. 319 - 324
• Main Authors: Ochi, Takehiro, Ohkubo, Yoshitaka, Mutoh, Seitaro
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 11-10-2002; Elsevier
• Subjects: 5-HT 2A receptor; 5-HT 3 receptor; Analgesics; Analgesics - chemistry; Analgesics - pharmacology; Animals; Antinociception; Biological and medical sciences; Descending serotonergic system; FR143166; Male; Medical sciences; Mice; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pain Measurement - drug effects; Pain Measurement - methods; Pharmacology. Drug treatments; Pyrazoles - chemistry; Pyrazoles - pharmacology; Receptors, Serotonin - metabolism; Serotonin - metabolism; Serotoninergic system; Spinal cord; Spinal Cord - drug effects; Spinal Cord - metabolism; Antinociception; Spinal cord; Descending serotonergic system; 5-HT 2A receptor; FR143166; 5-HT 3 receptor; 5-HT2A serotonin receptor; Rodentia; Central nervous system; Oral administration; Intrathecal administration; Hyperalgesia; Vertebrata; Mammalia; Analgesic; Pain; Mouse; Serotoninergic pathway; Animal; 5-HT3 Serotonine receptor; Pyrazole derivatives; Mechanism of action; Brain (vertebrata)
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(02)02334-8

We investigated the antinociceptive effect of 1-(4-fluorophenyl)-3-methyl-5-[4-(methylsulfinyl)phenyl]pyrazole (FR143166) in the tail-pinch test in mice. The p.o. and i.t. injection of FR143166 exerted dose-dependent antinociceptive actions with ED
50 values of 24 mg/kg and 15 μg/mouse, respectively. However, i.c.v. injection of FR143166 at a maximum dose of 128 μg/mouse did not show any antinociceptive effect. The antinociceptive effect of FR143166 injected i.t. was abolished by co-administration of the nonselective serotonin (5-hydroxytryptamine, 5-HT) receptor antagonist, methysergide, but not by the adrenoceptor antagonists, phentolamine and propranolol. Moreover, the effect of FR143166 was also reversed by the 5-HT
2A receptor antagonist, ketanserin, and the 5-HT
3 receptor antagonist, MDL-72222 (3-tropanyl-3,5-dichlorobenzoate). The effect of FR143166 was attenuated by
p-chlorophenylalanine, but not by 6-hydroxydopamine plus nomifensine pretreatment. These results suggest that the descending serotonergic system, especially spinal 5-HT
2A and 5-HT
3 receptors, is involved in the antinociceptive activity of spinally administered FR143166 on noxious mechanical stimuli.